title: Renal effects of NO-inhibition in patients with cirrhosis vs. healthy controls: a randomized placebo-controlled crossover study.
abstract: BACKGROUND
  Nitric oxide (NO) is an important regulator of renal hemodynamics and sodium excretion. Systemic and splanchnic NO-synthesis is increased in liver cirrhosis contributing to the characteristic hyperdynamic circulation. The significance of renal NO in human cirrhosis is not clear.
  
  
  OBJECTIVE
  In order to clarify the role of NO in the regulation of renal hemodynamics and sodium excretion in human cirrhosis, we studied the effects of N(G)-monomethyl-L-arginine (L-NMMA) - a nonselective NO-inhibitor - on blood pressure (MAP), heart rate (HR), GFR, RPF, UNa × V, FENa, FELi and plasma levels of renin, angII, aldo, ANP, BNP and cGMP in 13 patients with cirrhosis (Child gr.A: 8; Child gr.B+C: 5) and 13 healthy controls.
  
  
  METHODS
  The study was randomized and placebo-controlled. Renal hemodynamics were assessed by measuring renal clearance of (51) Cr-EDTA and (125) I-Hippuran for GFR and RPF, respectively.
  
  
  RESULTS
  L-NMMA induced a similar, significant increase in MAP in both groups and a more pronounced relative decrease in HR in the CIR group (P = 0.0209, anova). L-NMMA did not change GFR in any group, but RPF decreased significantly in both groups, but most pronouncedly in CIR (P = 0.0478, anova). FENa decreased significantly in both groups after l-NMMA, but the response was again most pronounced in the CIR group (P = 0.0270, anova). All parameters remained stable after placebo. No significant differences were observed between the effects of L-NMMA in Child gr.A vs. Child gr. B+C patients.
  
  
  CONCLUSIONS
  The data supports the hypothesis that renal NO is enhanced in human cirrhosis.
authors.affiliation: Department of Medical Research, Holstebro Hospital, Holstebro Denmark and Aarhus University, Aarhus, Denmark; Department of Medicine, Holstebro Hospital, Holstebro, Denmark.
authors.forename: Jesper N
authors.initials: JN
authors.lastname: Bech
authors.forename: Niels K
authors.initials: NK
authors.lastname: Aagaard
authors.forename: Robert S
authors.initials: RS
authors.lastname: Pedersen
authors.forename: Tina B
authors.initials: TB
authors.lastname: Sorensen
authors.forename: Hendrik
authors.initials: H
authors.lastname: Vilstrup
authors.forename: Erling B
authors.initials: EB
authors.lastname: Pedersen
mesh_terms: D000804:Angiotensin II / Q000097:blood; D018592:Cross-Over Studies; D003718:Denmark; D004492:Edetic Acid / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D007668:Kidney / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D017595:Renal Plasma Flow / Q000187:drug effects; D012083:Renin / Q000097:blood; D019323:omega-N-Methylarginine / Q000009:adverse effects* / Q000494:pharmacology*
chemical_list: D007457:Iodine Radioisotopes; D000804:Angiotensin II; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D004492:Edetic Acid; D019001:Nitric Oxide Synthase; D012083:Renin
keywords: cirrhosis; human; lithium; nitric oxide; omega-N-methylarginine; renal plasma flow; sodium